Blood-retina barrier dysfunction in experimental autoimmune uveitis: the pathogenesis and therapeutic targets / 대한해부학회지

Experimental autoimmune uveitis (EAU), an animal model of human uveitis, is characterized by infiltration of autoimmune T cells in the uvea as well as in the retina of susceptible animals. EAU is induced by the immunization of uveitogenic antigens, including either retinal soluble-antigen or interphotoreceptor retinoid-binding proteins, in Lewis rats. The pathogenesis of EAU in rats involves the proliferation of autoimmune T cells in peripheral lymphoid tissues and breakdown of the blood-retinal barrier, primarily in the uvea and retina, finally inducing visual dysfunction. In this review, we describe recent EAU studies to facilitate the design of a therapeutic strategy through the interruption of uveitogenic factors during the course of EAU, which will be helpful for controlling human uveitis.

Attenuation of Experimental Autoimmune Uveitis in Lewis Rats by Betaine

Experimental autoimmune uveitis (EAU) is an animal model of human autoimmune uveitis that is characterized by the infiltration of autoimmune T cells with concurrent increases in pro-inflammatory cytokines and reactive oxygen species. This study aimed to assess whether betaine regulates the progression of EAU in Lewis rats. EAU was induced via immunization with the interphotoreceptor retinoid-binding protein (IRBP) and oral administration of either a vehicle or betaine (100 mg/kg) for 9 consecutive days. Spleens, blood, and retinas were sampled from the experimental rats at the time of sacrifice and used for the T cell proliferation assay, serological analysis, real-time polymerase chain reaction, and immunohistochemistry. The T cell proliferation assay revealed that betaine had little effect on the proliferation of splenic T cells against the IRBP antigen in an in vitro assay on day 9 post-immunization. The serological analysis showed that the level of serum superoxide dismutase increased in the betainetreated group compared with that in the vehicle-treated group. The anti-inflammatory effect of betaine was confirmed by the downregulation of pro-inflammation-related molecules, including vascular cell adhesion molecule 1 and interleukin-1β in the retinas of rats with EAU. The histopathological findings agreed with those of ionized calcium-binding adaptor molecule 1 immunohistochemistry, further verifying that inflammation in the retina and ciliary bodies was significantly suppressed in the betaine-treated group compared with the vehicle-treated group. Results of the present study suggest that betaine is involved in mitigating EAU through anti-oxidation and anti-inflammatory activities.

Attenuation of Experimental Autoimmune Uveitis in Lewis Rats by Betaine

Experimental autoimmune uveitis (EAU) is an animal model of human autoimmune uveitis that is characterized by the infiltration of autoimmune T cells with concurrent increases in pro-inflammatory cytokines and reactive oxygen species. This study aimed to assess whether betaine regulates the progression of EAU in Lewis rats. EAU was induced via immunization with the interphotoreceptor retinoid-binding protein (IRBP) and oral administration of either a vehicle or betaine (100 mg/kg) for 9 consecutive days. Spleens, blood, and retinas were sampled from the experimental rats at the time of sacrifice and used for the T cell proliferation assay, serological analysis, real-time polymerase chain reaction, and immunohistochemistry. The T cell proliferation assay revealed that betaine had little effect on the proliferation of splenic T cells against the IRBP antigen in an in vitro assay on day 9 post-immunization. The serological analysis showed that the level of serum superoxide dismutase increased in the betainetreated group compared with that in the vehicle-treated group. The anti-inflammatory effect of betaine was confirmed by the downregulation of pro-inflammation-related molecules, including vascular cell adhesion molecule 1 and interleukin-1β in the retinas of rats with EAU. The histopathological findings agreed with those of ionized calcium-binding adaptor molecule 1 immunohistochemistry, further verifying that inflammation in the retina and ciliary bodies was significantly suppressed in the betaine-treated group compared with the vehicle-treated group. Results of the present study suggest that betaine is involved in mitigating EAU through anti-oxidation and anti-inflammatory activities.

Gene Expression Profile of Olfactory Transduction Signaling in an Animal Model of Human Multiple Sclerosis

Olfactory dysfunction occurs in multiple sclerosis in humans, as well as in an animal model of experimental autoimmune encephalomyelitis (EAE). The aim of this study was to analyze differentially expressed genes (DEGs) in olfactory bulb of EAE-affected mice by next generation sequencing, with a particular focus on changes in olfaction-related signals. EAE was induced in C57BL/6 mice following immunization with myelin oligodendrocyte glycoprotein and adjuvant. Inflammatory lesions were identified in the olfactory bulbs as well as in the spinal cord of immunized mice. Analysis of DEGs in the olfactory bulb of EAE-affected mice revealed that 44 genes were upregulated (and which were primarily related to inflammatory mediators), while 519 genes were downregulated; among the latter, olfactory marker protein and stomatin-like 3, which have been linked to olfactory signal transduction, were significantly downregulated (log2 [fold change] >1 and p-value < 0.05). These findings suggest that inflammation in the olfactory bulb of EAE-affected mice is associated with the downregulation of some olfactory signal transduction genes, particularly olfactory marker protein and stomatin-like 3, which may lead to olfactory dysfunction in an animal model of human multiple sclerosis.

Benefits of hesperidin in central nervous system disorders: a review / 대한해부학회지

Immunohistochemical localization of nerve injury-induced protein-1 in mouse tissues / 대한해부학회지

Amelioration of experimental autoimmune encephalomyelitis by Ishige okamurae / 대한해부학회지

Experimental autoimmune encephalomyelitis (EAE) is a T-cell-mediated autoimmune central nervous system disease characterized by inflammation with oxidative stress. The aim of this study was to evaluate an anti-inflammatory effect of Ishige okamurae on EAE-induced paralysis in rats. An ethanolic extract of I. okamurae significantly delayed the first onset and reduced the duration and severity of hind-limb paralysis. The neuropathological and immunohistochemical findings in the spinal cord were in agreement with these clinical results. T-cell proliferation assay revealed that the ethyl-acetate fraction of I. okamurae suppressed the proliferation of myelin basic protein reactive T cells from EAE affected rats. Flow cytometric analysis showed TCRαβ+ T cells was significantly reduced in the spleen of EAE rats with I. okamurae treatment with concurrent decrease of inflammatory mediators including tumor necrosis factor-α and cyclooxygenase-2. Collectively, it is postulated that I. okamurae ameliorates EAE paralysis with suppression of T-cell proliferation as well as decrease of pro-inflammatory mediators as far as rat EAE is concerned.

Potential involvement of glycogen synthase kinase (GSK)-3β in a rat model of multiple sclerosis: evidenced by lithium treatment / 대한해부학회지

Glycogen synthase kinase (GSK)-3β has been known as a pro-inflammatory molecule in neuroinflammation. The involvement of GSK-3β remains unsolved in acute monophasic rat experimental autoimmune encephalomyelitis (EAE). The aim of this study was to evaluate a potential role of GSK-3β in central nervous system (CNS) autoimmunity through its inhibition by lithium. Lithium treatment significantly delayed the onset of EAE paralysis and ameliorated its severity. Lithium treatment reduced the serum level of pro-inflammatory tumor necrosis factor a but not that of interleukin 10. Western blot analysis showed that the phosphorylation of GSK-3β (p-GSK-3β) and its upstream factor Akt was significantly increased in the lithium-treated group. Immunohistochemical examination revealed that lithium treatment also suppressed the activation of ionized calcium binding protein-1-positive microglial cells and vascular cell adhesion molecule-1 expression in the spinal cords of lithium-treated EAE rats. These results demonstrate that lithium ameliorates clinical symptom of acute monophasic rat EAE, and GSK-3 is a target for the suppression of acute neuroinflammation as far as rat model of human CNS disease is involved.

Lithium ameliorates rat spinal cord injury by suppressing glycogen synthase kinase-3β and activating heme oxygenase-1 / 대한해부학회지

Glycogen synthase kinase (GSK)-3β and related enzymes are associated with various forms of neuroinflammation, including spinal cord injury (SCI). Our aim was to evaluate whether lithium, a non-selective inhibitor of GSK-3β, ameliorated SCI progression, and also to analyze whether lithium affected the expression levels of two representative GSK-3β–associated molecules, nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) (a target gene of Nrf-2). Intraperitoneal lithium chloride (80 mg/kg/day for 3 days) significantly improved locomotor function at 8 days post-injury (DPI); this was maintained until 14 DPI (P<0.05). Western blotting showed significantly increased phosphorylation of GSK-3β (Ser9), Nrf-2, and the Nrf-2 target HO-1 in the spinal cords of lithium-treated animals. Fewer neuropathological changes (e.g., hemorrhage, inflammatory cell infiltration, and tissue loss) were observed in the spinal cords of the lithium-treated group compared with the vehicle-treated group. Microglial activation (evaluated by measuring the immunoreactivity of ionized calcium-binding protein-1) was also significantly reduced in the lithium-treated group. These findings suggest that GSK-3β becomes activated after SCI, and that a non-specific enzyme inhibitor, lithium, ameliorates rat SCI by increasing phosphorylation of GSK-3β and the associated molecules Nrf-2 and HO-1.

Appearance of osteoporosis in rat experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) in Lewis rats is characterized by transient paralysis followed by recovery. To evaluate whether transient paralysis in EAE affects bone density, tibiae of EAE rats were morphologically investigated using micro-computed tomography and histology. The parameters of bone health were significantly reduced at the peak stage of EAE rats relative to those of controls (p < 0.05). The reduction of bone density was found to remain unchanged, even in the recovery stage. Collectively, the present data suggest that osteoporosis occurs in paralytic rats with monophasic EAE, possibly through the disuse of hindlimbs and/or autoimmune inflammation.

Factors Associated with the Timeliness of Electronic Nursing Documentation / 대한의료정보학회지

OBJECTIVES: To investigate the factors associated with the timeliness of electronic nursing documentation using the entry time on the Electronic Medical Record (EMR) system. METHODS: As a retrospective study, data were extracted from January 1 to February 28, 2014 from a hospital EMR system and a nurses’ personnel information system. The timeliness of instances of nursing documentation was categorized into ‘timely’ or ‘untimely’ according to whether the entry time was time-stamped within the working hours during each day, evening, or night shift. Factors associated with the timeliness of the electronic nursing documentation were included in the logistic regression models as nurse- and patient-associated factors. RESULTS: Among 1,700,247 instances of electronic nursing documentation, 79.3% (n = 1,347,711) were completed within the working hours. Years of nursing experience, nursing shift, days of the week, patients’ age, and medical department had a statistically significant associated with the timeliness of nursing records. Nurses with experience of more than 1 year entered nursing records over 2 times more during their working hours than did less experienced nurses. During the evening and night shifts, nurses were 1.49 times and 9.19 times more likely to enter nursing documents in a timely manner, respectively, as compared to those in the day shift. CONCLUSIONS: Nursing documentation was typically completed outside of working hours when a nurse had little experience, worked during the day shift or weekdays, and when tasks were unpredictable. This shows that new nurses need support to familiarize them with various tasks and the overall workflow.

SMART Careplan System for Continuum of Care / 대한의료정보학회지

OBJECTIVES: This paper describes the integrated Careplan system, designed to manage and utilize the existing Electronic Medical Record (EMR) system; the system also defines key items for interdisciplinary communication and continuity of patient care. METHODS: We structured the Careplan system to provide effective interdisciplinary communication for healthcare services. The design of the Careplan system architecture proceeded in four steps-defining target datasets; construction of conceptual framework and architecture; screen layout and storyboard creation; screen user interface (UI) design and development, and pilot test and step-by-step deployment. This Careplan system architecture consists of two parts, a server-side and client-side area. On the server-side, it performs the roles of data retrieval and storage from target EMRs. Furthermore, it performs the role of sending push notifications to the client depending on the careplan series. Also, the Careplan system provides various convenient modules to easily enter an individual careplan. RESULTS: Currently, Severance Hospital operates the Careplan system and provides a stable service dealing with dynamic changes (e.g., domestic medical certification, the Joint Commission International guideline) of EMR. CONCLUSIONS: The Careplan system should go hand in hand with key items for strengthening interdisciplinary communication and information sharing within the EMR environment. A well-designed Careplan system can enhance user satisfaction and completed performance.

A study of animal bones excavated from the shell mound of Jeju Jongdali 1819 archaeological site / 대한수의학회지

Animal bones excavated with earthenware from the shell mound at the Jeju Jongdali 1819 archeological site, where three consecutive chronological layers covering the Neolithic (B.C. 15C-B.C. 10C), early Tamra, and late Tamra periods have been identified, were morphologically classified. The majority of the bones from all three periods were broken or split. The major fauna of the mammalian bones in all periods were Cervus spp., Sus scrofa, and Bos taurus. In the early and late Tamra periods, bones of small animals including Mustela sibirica coreana, Meles meles, Rodentia, and Aves were also found in small number. The excavated bones were from all parts of the animal bodies, including head, trunk, forelimb, and hindlimb. Collectively, these findings suggest that the major fauna from the Neolithic to late Tamra periods consisted of Cervus spp., Sus scrofa, and Bos taurus and that the fauna was dissected and carried to the shell mound site after hunting. Information from the bone remains in the shell mound are useful data for study of the wildlife and domestic animals living during the prehistoric period of Jeju Island.

Alternatively activated M2 macrophages increase in early stages of experimental autoimmune myocarditis in Lewis rats / 대한수의학회지

To better understand the role of macrophages in early stages of experimental autoimmune myocarditis (EAM), we compared the expression of inducible nitric oxide synthase (iNOS) and arginase-1, markers for classically activated M1 and alternatively activated M2 macrophages, respectively, in the hearts of EAM-affected and control rats. Immunohistochemical evidence revealed that both iNOS-positive and arginase 1-positive macrophages were found in EAM lesions, while some cells were co-localized with both markers. This finding suggests that the increased level of arginase-1, which is partly from M2 macrophages, contributes to the modulation of EAM, possibly through the reduction of nitric oxide in the lesion.

A morphological study of vomeronasal organ of Korean black goat (Capra aegagrus hircus) / 대한수의학회지

The vomeronasal organ (VNO) plays an important role in reproduction and social activities in ruminants including goats. A morphological study on the structure of VNO and its epithelial cells was carried out in Korean black goats. Grossly, the VNO of Korean goats opens into mouth through incisive ducts. Microscopically, the epithelium of VNO consisted of medial sensory epithelium and lateral non-sensory epithelium. Several blood vessels and nerve bundles were observed in the lamina propria encased by vomeronasal cartilage. Immunohistochemical staining showed that protein gene product (PGP) 9.5 was immunostained in the receptor cells of the sensory epithelium and in some cells of the non-sensory epithelium. Galectin-3 was mainly observed in the supporting cells of sensory and non-sensory epithelium. Lectins including wheat germ agglutinin, Ulex europaeus agglutinin, Bandeiraea simplicifolia lectin Isolectin B4, Dolichos biflorus agglutinin and soybean agglutinin used in this study were bound in VNO sensory, non-sensory epithelia as well as in the lamina propria with varying intensity. Collectively, this is a first descriptive morphological study of VNO of Korean black goat with special reference to lectin histochemistry.

Mechanism of experimental autoimmune encephalomyelitis in Lewis rats: recent insights from macrophages / 대한해부학회지

Experimental autoimmune encephalomyelitis (EAE) in Lewis rats is an acute monophasic paralytic central nervous system disease, in which most rats spontaneously recover from paralysis. EAE in Lewis rats is induced by encephalitogenic antigens, including myelin basic protein. EAE is mediated by CD4+ Th1 cells, which secrete pro-inflammatory mediators, and spontaneous recovery is mediated by regulatory T cells. Recently, it was established that classically activated macrophages (M1 phenotype) play an important role in the initiation of EAE, while alternatively activated macrophages (M2 phenotype) contribute to spontaneous recovery from rat EAE. This review will summarize the neuroimmunological aspects of active monophasic EAE, which manifests as neuroinflammation followed by neuroimmunomodulation and/or neuroprotection, with a focus on the role of alternatively activated macrophages.

Histochemical study of lectin-binding patterns in the rat vomeronasal organ during postnatal development / 대한수의학회지

Histochemical patterns of lectin binding during development of the rat vomeronasal organ (VNO) were studied to determine whether glycoconjugates are differently expressed after birth. Three types of lectins, Dolichos biflorus agglutinin (DBA), wheat germ agglutinin (WGA), and Ulex europaeus agglutinin I (UEA-I), were studied histochemically in the rat VNO at various stages post-birth: postnatal days 1 and 7, the preweaning period (4 weeks after birth), and at sexual maturity (8 weeks after birth). The free border of the vomeronasal sensory epithelium was positive for both WGA and UEA-I in rats of all ages; whereas, VNO receptor cells and supporting cells were positive only for both WGA and UEA-I from 4 weeks after birth. DBA reactivity was detected in the free border but less so in receptor cells and supporting cells. WGA and UEA-I, but not DBA, showed similar patterns in various ages. In the Jacobson's gland, WGA, UEA-I and DBA were detected in some acini from 4 weeks after birth but not at postnatal days 1 or 7. Collectively, reactivity for three lectins, WGA, UEA-I and DBA, increased in receptor cells and gland acini during postnatal development, possibly contributing to the enhanced chemoreception in rats.

Erythropoietin and autoimmune neuroinflammation: lessons from experimental autoimmune encephalomyelitis and experimental autoimmune neuritis / 대한해부학회지

Erythropoietin (EPO) is known to have numerous biological functions. While its primary function is during haematopoiesis, recent studies have shown that EPO plays important role in cytoprotection, immunomodulation, and antiapoptosis. These secondary functions of EPO are integral to tissue protection following hypoxic injury, ischemia-reperfusion injury, and spinal cord injury in the central nervous system. This review focuses on experimental evidence documenting the neuroprotective effects of EPO in organ-specific autoimmune nervous system disorders such as experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune neuritis (EAN). In addition, the immunomodulatory role of EPO in the pathogenesis of EAE and EAN animal models of human multiple sclerosis and Guillain-Barre syndrome, respectively, will be discussed.

Immunohistochemical localization of cyclic AMP-responsive element binding protein (CREB)-binding protein in the pig retina during postnatal development / 대한해부학회지

This study evaluated the cellular localization of cyclic AMP-responsive element binding protein-binding protein (CBP) expression in pig retinas during postnatal development. Immunohistochemistry and Western blot analysis were performed on retinal tissue from 2-day-old, 5-week-old, and 6-month-old pigs. Western blot analysis detected the expression of CBP in the retinas of 2-day-old piglets and showed that it was significantly decreased in the retinas of 5-week-old and 6-month-old pigs. Immunohistochemically, CBP was intensely immunostained in protein kinase C alpha (PKCalpha)-positive-bipolar cells, glutamine synthetase-positive Muller cells, and in ganglion cells in 2-day-old piglets. CBP was detected weakly in the inner plexiform, outer nuclear, and rod and cone layers. CBP immunoreactivity in the ganglion cell layer was decreased in the retinas of 5-week-old and 6-month-old pigs, while clear CBP expression detected in the neurite of PKCalpha-positive bipolar cells in the inner nuclear layer. In addition, CBP immunoreactivity in Muller cells and glial fibrillary acidic protein-positive glial processes was particularly noteworthy in pig retinas, but not in rat retinas. The results indicate that CBP is expressed differentially in the retinal neurons and glial cells according to growth and animal species, and may play an important role in homeostasis in Muller cells, neurite extention in bipolar cells, and signal transduction in photoreceptor cells in the porcine retina.

Protective effect of ethyl acetate extract of Ishige okamurae against carbon tetrachloride-induced acute liver injury in rats / 대한수의학회지

Several compounds and extracts isolated from a brown alga, Ishige (I.) okamurae, exhibit anti-oxidant and anti-inflammatory effects. The present study investigated whether the ethyl acetate (EtOAc) fraction of I. okamurae (EFIO) could ameliorate carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Sprague-Dawley rats were intraperitoneally (i.p.) administered with EFIO at 10 or 50 mg/kg per day for 2 consecutive days before CCl4 injection (3.3 mL/kg, i.p.). Twenty four hours later, the rats were anesthesized with diethyl ether and dissected. Pretreatment with EFIO significantly reduced the increased serum levels of alanine aminotransferase and aspartate aminotransferase in CCl4-treated rats. Pretreatment with EFIO also significantly inhibited the reduced activities of superoxide dismutase and catalase in the CCl4-injured liver. Histopathological evaluations showed that hemorrhage, hepatocyte necrosis, inflammatory cell infiltration, and fatty degeneration induced by CCl4 treatment were ameliorated by the administration of EFIO. Additionally, liver immunohistochemical analyses revealed the marked reduction in ED1-positive monocyte-like macrophages in EFIO-pretreated rats given CCl4. These results suggest that EFIO ameliorates CCl4-induced liver injury, possibly through the inhibition of oxidative stress.